Since their initial conception approximately fourteen years ago, active-matrix flat-panel imagers (AMFPIs) have undergone extensive research and development. Our prior NIH-sponsored research efforts (for which this is a competing renewal), along with the efforts of others, have directly contributed toward the recent commercial introduction of the technology to external beam, radiotherapy portal imaging in clinical environments. AMFPIs represent a highly compact, large area (presently up to 40x40 cm2), solid-state technology that can be operated both radiographically and fluoroscopically. They offer substantially improved image quality at radiotherapy energies compared to that of the previous "gold standard," film (which itself provides image quality superior to that of other electronic portal imaging technologies). However, AMFPIs, like all commercially available portal imaging technologies, make use of only -1 percent of the incident radiation. The result is that the frequency-dependent detective quantum efficiency (DQE - a widely accepted observer-independent measure of imager performance) of AMFPIs, although higher than that of other commercial portal imaging technologies, is still only 1 percent. Thus, even though current AMFPIs provide radiotherapy images with a fairly high degree of spatial and contrast information content, significant improvements in image quality and DQE are possible, allowing improved clinical utility and new uses. Consequently, the hypothesis to be examined in the proposed research is: "Through the incorporation of innovative strategies, the DQE of radiotherapy AMFPIs can be substantially increased through more efficient use of the incident radiation." Three approaches for increasing DQE will be examined, all of which offer the potential of increasing the percentage of the beam interacting with the imager while minimizing degradation of spatial resolution. Two approaches involve indirect detection of the incident radiation (using segmented scintillating converters employing CsI(Tl) and GcI2O2S:Th) while a third approach involves direct detection of the radiation (using relatively thick layers of HgI2 photoconductive material). This three-year project, if successful, would identify the most promising strategy to substantially increase the DQE, potentially in excess of a factor of 10, and conceivably leading to significant improvements in image quality, even at very low doses.